A solid-state NMR study of molecular mobility and phase separation in co-spray-dried protein脙脙脙脙脙脙sugar particles
- 作者：Suihko ; Eero J. ; Forbes ; Robert T. ; Apperley ; David C.
- 关键词：Protein formulation ; Spray-drying ; Solid-state NMR ; Molecular mobility ; Phase separation
- 刊名：European Journal of Pharmaceutical Sciences
- 出版年：2005
- 期刊代码：15_09280987
- 类别：pha
- 出版时间：May, 2005
- 卷：25
- 期：1
- 页码：105-112
- 文件大小：219 K
摘要
Molecular mobility and physical form of co-spray-dried sugar–lysozyme formulations were evaluated. Co-spray-dried trehalose:lysozyme and sucrose:lysozyme formulations in 1:9, 1:1 and 9:1 ratios (w:w) were stored at 0%RH and 75%RH for 5–6 days. Molecular mobility and physical form of the co-spray-dried formulations after storage were determined by using 13C and 1H solid-state NMR as well as X-ray powder diffractometry. The results showed that increasing sugar content in co-spray-dried formulations stored at 0%RH decreased molecular mobility of the amorphous formulations indicating a close association of the protein and sugar. Exposure of sugar–lysozyme 1:1 and 9:1 formulations to 75%RH led to separation of sugar and protein phases, where the sugar phase was crystalline. The intimate sugar–lysozyme interaction of the formulations stored at 0%RH and the phase separation of the sugar-rich formulations stored at 75%RH were also confirmed by using 13C solid-state NMR spin-lattice relaxation time-filter (T1-filter) measurements. The propensity of sucrose and trehalose to crystallise was similar; however, the results suggest that part of the sugar in the phase-separated formulations remained amorphous and in close association with lysozyme.